Intracellular osteopontin protects from autoimmunity-driven lymphoma development inhibiting TLR9-MYD88-STAT3 signaling.
Humans
Mice
Animals
Mice, Inbred MRL lpr
Mice, Inbred C57BL
Lupus Erythematosus, Systemic
/ genetics
Autoimmune Diseases
Signal Transduction
Adaptor Proteins, Signal Transducing
/ metabolism
Lymphoma
/ genetics
Toll-Like Receptor 9
/ metabolism
STAT3 Transcription Factor
/ metabolism
Myeloid Differentiation Factor 88
/ genetics
Autoimmunity
Diffuse large B cell lymphoma
Osteopontin
Journal
Molecular cancer
ISSN: 1476-4598
Titre abrégé: Mol Cancer
Pays: England
ID NLM: 101147698
Informations de publication
Date de publication:
12 Dec 2022
12 Dec 2022
Historique:
received:
27
04
2022
accepted:
28
11
2022
entrez:
12
12
2022
pubmed:
13
12
2022
medline:
15
12
2022
Statut:
epublish
Résumé
Autoimmune disorders, including Systemic Lupus Erythematosus (SLE), are associated with increased incidence of hematological malignancies. The matricellular protein osteopontin (OPN) has been linked to SLE pathogenesis, as SLE patients show increased serum levels of OPN and often polymorphisms in its gene. Although widely studied for its pro-tumorigenic role in different solid tumours, the role of OPN in autoimmunity-driven lymphomagenesis has not been investigated yet. To test the role of OPN in the SLE-associated lymphomagenesis, the SLE-like prone Fas Despite reduced autoimmunity signs, OPN-/-Fas These data indicate that, in the setting of SLE-like syndrome in which double strand-DNA chronically circulates and activates TLRs, B cell intracellular OPN exerts a protective role in autoimmunity-driven DLBCL development, mainly acting as a brake in the TLR9-MYD88-STAT3 signaling pathway.
Sections du résumé
BACKGROUND
BACKGROUND
Autoimmune disorders, including Systemic Lupus Erythematosus (SLE), are associated with increased incidence of hematological malignancies. The matricellular protein osteopontin (OPN) has been linked to SLE pathogenesis, as SLE patients show increased serum levels of OPN and often polymorphisms in its gene. Although widely studied for its pro-tumorigenic role in different solid tumours, the role of OPN in autoimmunity-driven lymphomagenesis has not been investigated yet.
METHODS
METHODS
To test the role of OPN in the SLE-associated lymphomagenesis, the SLE-like prone Fas
RESULTS
RESULTS
Despite reduced autoimmunity signs, OPN-/-Fas
CONCLUSION
CONCLUSIONS
These data indicate that, in the setting of SLE-like syndrome in which double strand-DNA chronically circulates and activates TLRs, B cell intracellular OPN exerts a protective role in autoimmunity-driven DLBCL development, mainly acting as a brake in the TLR9-MYD88-STAT3 signaling pathway.
Identifiants
pubmed: 36503430
doi: 10.1186/s12943-022-01687-6
pii: 10.1186/s12943-022-01687-6
pmc: PMC9743519
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
TLR9 protein, human
0
Toll-Like Receptor 9
0
STAT3 protein, human
0
STAT3 Transcription Factor
0
Myd88 protein, mouse
0
Myeloid Differentiation Factor 88
0
Tlr9 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
215Informations de copyright
© 2022. The Author(s).
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